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PMID:18434417

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Citation

Miura, GI, Roignant, JY, Wassef, M and Treisman, JE (2008) Myopic acts in the endocytic pathway to enhance signaling by the Drosophila EGF receptor. Development 135:1913-22

Abstract

Endocytosis of activated receptors can control signaling levels by exposing the receptors to novel downstream molecules or by instigating their degradation. Epidermal growth factor receptor (EGFR) signaling has crucial roles in development and is misregulated in many cancers. We report here that Myopic, the Drosophila homolog of the Bro1-domain tyrosine phosphatase HD-PTP, promotes EGFR signaling in vivo and in cultured cells. myopic is not required in the presence of activated Ras or in the absence of the ubiquitin ligase Cbl, indicating that it acts on internalized EGFR, and its overexpression enhances the activity of an activated form of EGFR. Myopic is localized to intracellular vesicles adjacent to Rab5-containing early endosomes, and its absence results in the enlargement of endosomal compartments. Loss of Myopic prevents cleavage of the EGFR cytoplasmic domain, a process controlled by the endocytic regulators Cbl and Sprouty. We suggest that Myopic promotes EGFR signaling by mediating its progression through the endocytic pathway.

Links

PubMed PMC2413058 Online version:10.1242/dev.017202

Keywords

Amino Acid Sequence; Animals; Blotting, Western; Cell Line; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/physiology; Drosophila melanogaster/cytology; Drosophila melanogaster/embryology; Drosophila melanogaster/genetics; Endocytosis/genetics; Endocytosis/physiology; Endosomes/metabolism; Eye/cytology; Eye/embryology; Eye/metabolism; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Immunohistochemistry; Membrane Proteins/metabolism; Models, Biological; Molecular Sequence Data; Photoreceptor Cells, Invertebrate/cytology; Photoreceptor Cells, Invertebrate/embryology; Photoreceptor Cells, Invertebrate/metabolism; Proto-Oncogene Proteins c-cbl/metabolism; Receptor, Epidermal Growth Factor/genetics; Receptor, Epidermal Growth Factor/metabolism; Receptor, Epidermal Growth Factor/physiology; Signal Transduction/genetics; Signal Transduction/physiology; Transfection; ras Proteins/genetics; ras Proteins/metabolism; ras Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q9VUH6

located_in

GO:0031982: vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9VUH6

involved_in

GO:0046534: positive regulation of photoreceptor cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VUH6

involved_in

GO:0045742: positive regulation of epidermal growth factor receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0003205

P

Seeded From UniProt

complete


See also

References

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